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K. Hayakawa



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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-028 - High Vimentin Expression in Micropapillary Component of Lung Adenocarcinomas (ID 1140)

      09:30 - 17:00  |  Author(s): K. Hayakawa

      • Abstract
      • Slides

      Background:
      It is increasingly being recognized that adenocarcinomas (AC) of various organs with tumor cells arranged in a micropapillary pattern are more malignant than those without such a micropapillary component (MPC). However, the factors and mechanisms conferring the increased malignancy on MPC remain to be elucidated, so the exploration of such factors was the main purpose of the present study.

      Methods:
      We histologically reviewed the 629 radically resected lung adenocarcinomas at Kitasato University Hospital, Japan, from January 2002 to December 2012. MPC was defined as a small papillary tumor cell tuft without an obvious fibrovascular core. Tumors with ≥ 1% of their tumor cells arranged in a micropapillary pattern were diagnosed as AC with MPC (AC-MPC), while the remainder were diagnosed as conventional AC (CAC). The histological subtypes and differentiation grade of CAC as well as the background non-MPC of the AC-MPE were determined according to the 4th WHO classification. The clinicopathological features of AC-MPC and CAC were comparatively studied. The specific proteins expressed in AC-MPC were also analyzed using proteomic study based on 2-dimensional gel electrophoresis (2-DE), and the results were confirmed in vivo with imunohistochemistry.

      Results:
      One hundred and one (16.1%) of the 629 histologically reviewed lung adenocarcinomas met the criteria defined above and were thus diagnosed as AC-MPC. Compared with the CAC, the AC-MPC had worse statuses for tumor size, vascular invasion, pleural invasion, node metastasis, disease stage, postoperative up-staging, and overall survival (OS) and disease-free survival (DFS) (p<0.0001, respectively). On 2-DE, 19 proteins differentially expressed more than 1.5-fold in amount between lung CAC and AC-MPC; in particular, vimentin, one of the identified proteins, was most up-regulated (3.5-fold) in AC-MPC cases. Vimentin expression was detected in MPC of 95 (94.1%) AC-MPC, and when compared with the 119 control CAC, the expression scores in MPC were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (p<0.0001), but not significantly different from those of poorly differentiated CAC (p=0.561). Within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis, and multivariate analysis showed that high vimentin expression was an independent indicator of worse prognosis (OS: p=0.012, DFS: p=0.047).

      Conclusion:
      Vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

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